Arrhythmogenic left ventricular cardiomyopathy is a genetic myocardial disease difficult to diagnose due to the lack of gold standard criteria. Simultaneous PET/MR imaging, combined with multiparametric quantitative analysis, could facilitate the identification of different profiles related to the phenotype and progression of cardiomyopathy. This preliminary study focuses on a methodological strategy for dealing with PET/MRI data, including inter-patient data linkage and regional analysis. Two-step clustering was applied to T1 and T2 maps, LGE, and 18F-FDG-PET images of 99 patients genetically diagnosed with arrhythmogenic left ventricular cardiomyopathy. Each patient's images were independently z-scored and summed into a single volume, which was clustered into supervoxels. Thirty-two inter-patient groups of supervoxels were obtained by spectral clustering. An "abnormality" score was assigned to each cluster and modality, and used to visualise abnormal regions likely associated with disease. They enabled the generation of automated textual and bullseye health reports for each patient, which were compared with cardiac imager assessments using balanced accuracy in repeated nested cross-validation. This approach was further validated on a larger cohort of 167 numerical phantoms. The reports generated by clustering accurately identified most of the cardiac physicians' observations (BA = 0.76 ± 0.04 in repeated nested cross-validation on patients, and BA ≥ 0.8 on phantoms). Furthermore, the identified abnormal clusters closely matched their visual observations, facilitating the identification of varying degrees of fibrosis or inflammation on the images. This approach enables a more systematic handling of multimodal PET/MRI data to characterise myocardial heterogeneity in arrhythmogenic left ventricular cardiomyopathy patients.

Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) results in better sensitivity for prosthetic valve endocarditis (PVE) diagnosis, but visual image analysis results in relatively weak specificity and significant interobserver variability.The primary objective of this study was to evaluate the performance of a radiomics and machine learning-based analysis of 18F-FDG PET/CT (PET-ML) as a major criterion for the European Society of Cardiology score using machine learning as a major imaging criterion (ESC-ML) in PVE diagnosis. The secondary objective was to assess performance of PET-ML as a standalone examination.All 18F-FDG-PET/CT scans performed for suspected aortic PVE at a single center from 2015 to 2021 were retrospectively included. The gold standard was expert consensus after at least 3 months' follow-up. The machine learning (ML) method consisted of manually segmenting each prosthetic valve, extracting 31 radiomics features from the segmented region, and training a ridge logistic regressor to predict PVE. Training and hyperparameter tuning were done with a cross-validation approach, followed by an evaluation on an independent test database.A total of 108 patients were included, regardless of myocardial uptake, and were divided into training (n = 68) and test (n = 40) cohorts. Considering the latter, PET-ML findings were positive for 13 of 22 definite PVE cases and 3 of 18 rejected PVE cases (59% sensitivity, 83% specificity), thus leading to an ESC-ML sensitivity of 72% and a specificity of 83%.The use of ML for analyzing 18F-FDG-PET/CT images in PVE diagnosis was feasible and beneficial, particularly when ML was included in the ESC 2015 criteria. Despite some limitations and the need for future developments, this approach seems promising to optimize the role of 18F-FDG PET/CT in PVE diagnosis.

Two examples of Î"SUVmax measurements in patients with multiple myeloma on FDG-PET scans acquired at baseline and after three courses of RVD

Background: Fluorine-18 fluorodeoxyglucose (F-18-FDG)-positron emission tomography (PET)/computed tomography (CT) results in better sensitivity for prosthetic valve endocarditis (PVE) diagnosis, but visual image analysis results in relatively weak specificity and significant interobserver variability.Objectives: The primary objective of this study was to evaluate the performance of a radiomics and machine learning-based analysis of F-18-FDG PET/CT (PET-ML) as a major criterion for the European Society of Cardiology score using machine learning as a major imaging criterion (ESC-ML) in PVE diagnosis. The secondary objective was to assess performance of PET-ML as a standalone examination.Methods: All F-18-FDG-PET/CT scans performed for suspected aortic PVE at a single center from 2015 to 2021 were retrospectively included. The gold standard was expert consensus after at least 3 months' follow-up. The machine learning (ML) method consisted of manually segmenting each prosthetic valve, extracting 31 radiomics features from the segmented region, and training a ridge logistic regressor to predict PVE. Training and hyperparameter tuning were done with a cross-validation approach, followed by an evaluation on an independent test database.Results: A total of 108 patients were included, regardless of myocardial uptake, and were divided into training (n = 68) and test (n = 40) cohorts. Considering the latter, PET-ML findings were positive for 13 of 22 definite PVE cases and 3 of 18 rejected PVE cases (59% sensitivity, 83% specificity), thus leading to an ESC-ML sensitivity of 72% and a specificity of 83%.Conclusions: The use of ML for analyzing F-18-FDG-PET/CT images in PVE diagnosis was feasible and beneficial, particularly when ML was included in the ESC 2015 criteria. Despite some limitations and the need for future developments, this approach seems promising to optimize the role of F-18-FDG PET/CT in PVE diagnosis.

HomeCirculation: Cardiovascular ImagingVol. 15, No. 718F-Fluorodeoxyglucose Positron Emission Tomography for the Detection of Myocardial Inflammation in Arrhythmogenic Left Ventricular Cardiomyopathy Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUB18F-Fluorodeoxyglucose Positron Emission Tomography for the Detection of Myocardial Inflammation in Arrhythmogenic Left Ventricular Cardiomyopathy Roxane Tessier, Lara Marteau, Marc Vivien, Béatrice Guyomarch, Aurélie Thollet, Imen Fellah, Bastien Jamet, Jean Charles Sébille, Thomas Eugene, Jean Michel Serfaty, Vincent Probst, Jean Noël Trochu, Claire Toquet, Karine Warin-Fresse and Nicolas Piriou Roxane TessierRoxane Tessier CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. , Lara MarteauLara Marteau https://orcid.org/0000-0002-4904-1810 CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. Department of Cardiovascular Radiology (L.M., J.M.S., K.W.-F.), CHU Nantes, Nantes Université, France. , Marc VivienMarc Vivien CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. , Béatrice GuyomarchBéatrice Guyomarch CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. , Aurélie TholletAurélie Thollet CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. , Imen FellahImen Fellah CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. , Bastien JametBastien Jamet Department of Nuclear Medicine (B.J., J.C.S., T.E., N.P.), CHU Nantes, Nantes Université, France. , Jean Charles SébilleJean Charles Sébille https://orcid.org/0000-0002-8234-6456 Department of Nuclear Medicine (B.J., J.C.S., T.E., N.P.), CHU Nantes, Nantes Université, France. , Thomas EugeneThomas Eugene Department of Nuclear Medicine (B.J., J.C.S., T.E., N.P.), CHU Nantes, Nantes Université, France. , Jean Michel SerfatyJean Michel Serfaty Department of Cardiovascular Radiology (L.M., J.M.S., K.W.-F.), CHU Nantes, Nantes Université, France. , Vincent ProbstVincent Probst https://orcid.org/0000-0002-5492-8619 CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. , Jean Noël TrochuJean Noël Trochu https://orcid.org/0000-0003-4742-281X CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. , Claire ToquetClaire Toquet CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. Department of Pathology (C.T.), CHU Nantes, Nantes Université, France. , Karine Warin-FresseKarine Warin-Fresse Department of Cardiovascular Radiology (L.M., J.M.S., K.W.-F.), CHU Nantes, Nantes Université, France. and Nicolas PiriouNicolas Piriou Correspondence to: Nicolas Piriou, MD, Service de Médecine Nucléaire, CHU de Nantes, Hôpital Laënnec, 44093 Nantes Cedex 1, France. Email E-mail Address: [email protected] https://orcid.org/0000-0002-6677-6552 CNRS, INSERM, l'institut du thorax (R.T., L.M., M.V., B.G., A.T., I.F., V.P., J.N., C.T., N.P.), CHU Nantes, Nantes Université, France. Department of Nuclear Medicine (B.J., J.C.S., T.E., N.P.), CHU Nantes, Nantes Université, France. Originally published30 Jun 2022https://doi.org/10.1161/CIRCIMAGING.122.014065Circulation: Cardiovascular Imaging. 2022;15Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 30, 2022: Ahead of Print In recently updated classification and diagnostic criteria for arrhythmogenic cardiomyopathy (AC), presence of subepicardial or midmyocardial late gadolinium enhancement (LGE) of septal, inferior, or lateral left ventricular (LV) walls on cardiac magnetic resonance (CMR; Figure [A]) is one of the 2 major diagnostic criteria for arrhythmogenic LV cardiomyopathy (ALVC), a particular AC phenotype with isolated or predominant LV involvement.1 Evidence of a pathogenic genetic variant is required to confirm the diagnosis of the genetic syndrome. Some studies have shown that myocarditis and chronic myocardial inflammation can be associated to ALVC.2 Apart from endomyocardial biopsy, diagnosing myocardial inflammation associated to ALVC is challenging. In CMR, LGE is strongly suggestive of fibrotic replacement associated to AC, but tissue characterization tools are known to be less sensitive to distinguish between LGE only due to fibrosis or associated to inflammation in arrhythmogenic and cardiomyopathic clinical presentations of myocarditis.3 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), widely used in cardiac sarcoidosis, could be of interest to increase imaging sensitivity in detecting myocardial inflammation in ALVC.Download figureDownload PowerPointFigure. Comparison of contrast-enhanced cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) findings in arrhythmogenic left ventricular cardiomyopathy (ALVC). A, Contrast-enhanced CMR (left) and FDG-PET (right) in a patient with DSP (desmoplakin) pathogenic variant. CMR shows typical features of ALVC with subepicardial late gadolinium enhancement (LGE) on lateral and inferior left ventricular (LV) walls and midmyocardial LGE of the inferoseptal wall. PET shows concordant FDG uptake in corresponding areas with subepicardial LGE. B, Bulls eyes representations of the percentages of patients with subepicardial LGE (left) and FDG uptake (right) for each LV segment.We retrospectively analyzed data from 17 patients with a final diagnosis of ALVC who had benefited from a cardiac FDG-PET scan after prolonged fasting and low carbohydrates diet to suppress physiological cardiomyocytes glucose uptake, so that residual myocardial FDG hypermetabolism can reflect areas of myocardial inflammation. FDG-PET was performed in the course of routine diagnostic work-up to rule out phenocopies such as nonhereditary inflammatory AC. The study was approved by the institutional review committee and participants gave informed consent. The data that support the findings of this study are available from the corresponding author upon reasonable request.Seventy-one percent of patients were women, mean age was 45±14 years. Mean LVEF was 42±15%. Genetic variants were classified as pathogenic following the 5-tier terminology system of the American College of Medical Genetics and Genomics.4 DSP, coding for the desmosomal protein Desmoplakin, was the most common gene involved (n=10; 59%). Other genotypes were PKP2 (plakophilin-2 [desmosome], n=2), FLNC (filamin C [cytoskeleton], n=2), LMNA (lamin A/C [nuclear envelope], n=1), DES (desmin ([intermediate filament], n=1), Ryr2 (ryanodine receptor 2 [sarcoplasmic reticulum], n=1). Five patients (31%) had a previous history of myocarditis.Ten out of 17 patients had a significant LV myocardial FDG uptake assessed visually. FDG uptake pattern was focal in 7 patients (Figure [A]), diffuse in 3. LVEF was not significantly different between patients with and patients without LV FDG (respectively 38±14%, n=10, and 47±15%, respectively, n=7, P=0.22, Mann-Whitney U test). Myocarditis was significantly associated with the presence of FDG uptake (n=5/10 patients with FDG uptake had a history of myocarditis, n=0/7 patients without FDG uptake, P=0.04, Fisher exact test). Two patients with clinically suspected myocarditis had an endomyocardial biopsy that revealed no signs of myocardial inflammation but cardiomyocyte dystrophy and fibrosis.Mixed logistic models with random effects showed that FDG uptake was significantly more present on lateral and inferior LV walls (P=0.037; Figure [B]). There was a weak correlation between the presence of FDG and subepicardial or midmyocardial locations of LGE on CMR in the same segment (Spearman correlation coefficient ρ=0.44; P=0.08). For subepicardial-only LGE locations (111 segments/289 total), the presence of FDG uptake in a segment was significantly correlated with the presence of LGE (ρ=0.71; P=0.01; Figure [B]).Significant co-location of FDG uptake and subepicardial LGE in LV lateral and inferior walls, a typical CMR feature of myocarditis, as well as the consistent FDG positivity in patients with previous history of myocarditis, suggest that FDG-PET could be of interest to noninvasively detect sub-acute or chronic myocardial inflammation in patients with ALVC.This largest reported sample of patients with ALVC with FDG-PET myocardial characterization carries several limitations. FDG-PET indication was based on clinical or CMR findings suggestive of an inflammatory cardiomyopathy representing a selection bias. FDG-PET and CMR interpretation were not blinded. In the absence of control group and pathological correlation in all patients, FDG uptake may reflect nonspecific findings associated to insufficient physiological uptake suppression or myocardial metabolic shift due to several pathological conditions. Two patients had negative endomyocardial biopsy that do not necessarily mean that FDG avidity was not because of myocardial inflammation as they were performed on the RV side of the septum whereas FDG uptake was located on the lateral LV walls in both patients, as in the whole cohort.Given increasing evidences that inflammation plays a role in AC,5 we think that these results must encourage further prospective studies with consecutive ALVC patients to determine whether FDG-PET can become a routine imaging tool to noninvasively detect myocardial inflammation.Article InformationSources of FundingNone.Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page 562.Correspondence to: Nicolas Piriou, MD, Service de Médecine Nucléaire, CHU de Nantes, Hôpital Laënnec, 44093 Nantes Cedex 1, France. Email nicolas.piriou@chu-nantes.frReferences1. Corrado D, Zorzi A, Cipriani A, Bauce B, Bariani R, Beffagna G, De Lazzari M, Migliore F, Pilichou K, Rampazzo A, et al. Evolving diagnostic criteria for arrhythmogenic cardiomyopathy.J Am Heart Assoc. 2021; 10:e021987. doi: 10.1161/JAHA.121.021987LinkGoogle Scholar2. Smith ED, Lakdawala NK, Papoutsidakis N, Aubert G, Mazzanti A, McCanta AC, Agarwal PP, Arscott P, Dellefave-Castillo LM, Vorovich EE, et al. Desmoplakin cardiomyopathy, a fibrotic and inflammatory form of cardiomyopathy distinct from typical dilated or arrhythmogenic right ventricular cardiomyopathy.Circulation. 2020; 141:1872–1884. doi: 10.1161/CIRCULATIONAHA.119.044934LinkGoogle Scholar3. Francone M, Chimenti C, Galea N, Scopelliti F, Verardo R, Galea R, Carbone I, Catalano C, Fedele F, Frustaci A. CMR sensitivity varies with clinical presentation and extent of cell necrosis in biopsy-proven acute myocarditis.JACC Cardiovasc Imaging. 2014; 7:254–263. doi: 10.1016/j.jcmg.2013.10.011CrossrefMedlineGoogle Scholar4. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al; ACMG Laboratory Quality Assurance Committee.Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med. 2015; 17:405–424. doi: 10.1038/gim.2015.30CrossrefMedlineGoogle Scholar5. Asatryan B, Asimaki A, Landstrom AP, Khanji MY, Odening KE, Cooper LT, Marchlinski FE, Gelzer AR, Semsarian C, Reichlin T, et al. Inflammation and immune response in arrhythmogenic cardiomyopathy: state-of-the-art review.Circulation. 2021; 144:1646–1655. doi: 10.1161/CIRCULATIONAHA.121.055890LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Protonotarios A and Wicks E (2023) The role of FDG-PET imaging in arrhythmogenic cardiomyopathy, International Journal of Cardiology, 10.1016/j.ijcard.2023.131275, 391, (131275), Online publication date: 1-Nov-2023. Arbelo E, Protonotarios A, Gimeno J, Arbustini E, Barriales-Villa R, Basso C, Bezzina C, Biagini E, Blom N, de Boer R, De Winter T, Elliott P, Flather M, Garcia-Pavia P, Haugaa K, Ingles J, Jurcut R, Klaassen S, Limongelli G, Loeys B, Mogensen J, Olivotto I, Pantazis A, Sharma S, Van Tintelen J, Ware J, Kaski J, Charron P, Imazio M, Abdelhamid M, Aboyans V, Arad M, Asselbergs F, Asteggiano R, Bilinska Z, Bonnet D, Bundgaard H, Cardim N, Čelutkienė J, Cikes M, De Ferrari G, Dusi V, Falk V, Fauchier L, Gandjbakhch E, Heliö T, Koskinas K, Kotecha D, Landmesser U, Lazaros G, Lewis B, Linhart A, Løchen M, Meder B, Mindham R, Moon J, Nielsen J, Petersen S, Prescott E, Sheppard M, Sinagra G, Sitges M, Tfelt-Hansen J, Touyz R, Veltrop R, Veselka J, Wahbi K, Wilde A, Zeppenfeld K, Kichou B, Sisakian H, Scherr D, Gerber B, Džubur A, Gospodinova M, Planinc I, Moustra H, Zemánek D, Jensen M, Samir A, Palm K, Heliö T, Wahbi K, Schulze-Bahr E, Haralambos V, Sepp R, Aðalsteinsdóttir B, Ward D, Blich M, Sinagra G, Poniku A, Lunegova O, Rudzitis A, Kassab R, Barysienė J, Huijnen S, Felice T, Vataman E, Pavlovic N, Doghmi N, Asselbergs F, Kostovska E, Almaas V, Biernacka E, Brito D, Rosca M, Zavatta M, Ristic A, Goncalvesová E, Šinkovec M, Cañadas-Godoy V, Platonov P, Saguner A, Saadi A, Kammoun I, Celik A, Nesukay E, Abdullaev T, Prescott E, James S, Arbelo E, Baigent C, Borger M, Buccheri S, Ibanez B, Køber L, Koskinas K, McEvoy J, Mihaylova B, Mindham R, Neubeck L, Nielsen J, Pasquet A, Rakisheva A, Rocca B, Rossello X, Vaartjes I, Vrints C, Witkowski A and Zeppenfeld K (2023) 2023 ESC Guidelines for the management of cardiomyopathies, European Heart Journal, 10.1093/eurheartj/ehad194, 44:37, (3503-3626), Online publication date: 1-Oct-2023. Bevan G, Lal M and Nazer B (2023) Nonischemic Cardiomyopathy, JACC: Basic to Translational Science, 10.1016/j.jacbts.2023.08.010, 8:10, (1395-1396), Online publication date: 1-Oct-2023. Torbey A, Nascimento E, Nunes N, Carvalho A, Neves D, Couto R, Pimentel S, Maia E and Mesquita E (2023)(2023)(2023)(2023) Arrhythmogenic Left Ventricular Cardiomyopathy – State of Art: From Genotype to Phenotype, ABC Heart Fail Cardiomyop, 10.36660/abchf.20230035, 3:1, Online publication date: 29-Aug-2023., Online publication date: 29-Aug-2023., Online publication date: 1-Aug-2023., Online publication date: 1-Aug-2023. Kober F (2023) Noninvasive Cardiovascular Imaging in Preclinical Research, JACC: Basic to Translational Science, 10.1016/j.jacbts.2023.02.009, 8:7, (817-819), Online publication date: 1-Jul-2023. Lazzeroni D, Crocamo A, Ziveri V, Notarangelo M, Rizzello D, Spoladori M, Donelli D, Cacciola G, Ardissino D, Niccoli G and Peretto G (2023) Personalized Management of Sudden Death Risk in Primary Cardiomyopathies: From Clinical Evaluation and Multimodality Imaging to Ablation and Cardioverter-Defibrillator Implant, Journal of Personalized Medicine, 10.3390/jpm13050877, 13:5, (877) Monda E, Rubino M, Palmiero G, Verrillo F, Lioncino M, Diana G, Cirillo A, Fusco A, Dongiglio F, Caiazza M, Altobelli I, Mauriello A, Guarnaccia N, Scatteia A, Cesaro A, Pacileo G, Sarubbi B, Frisso G, Bauce B, D'Andrea A, Dellegrottaglie S, Russo M, Calabrò P and Limongelli G (2023) Multimodality Imaging in Arrhythmogenic Left Ventricular Cardiomyopathy, Journal of Clinical Medicine, 10.3390/jcm12041568, 12:4, (1568) July 2022Vol 15, Issue 7 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.122.014065PMID: 35770631 Originally publishedJune 30, 2022 Keywordsarrhythmogenic cardiomyopathyinflammationMRImyocarditisPET-CTPDF download Advertisement SubjectsCardiomyopathyGeneticsInflammatory Heart DiseaseNuclear Cardiology and PET

The aims of this multicenter study were to identify clinical and preoperative PET/CT parameters predicting overall survival (OS) and distant metastasis-free survival (DMFS) in a cohort of head and neck squamous cell carcinoma patients treated with surgery, to generate a prognostic model of OS and DMFS, and to validate this prognostic model with an independent cohort. Methods: A total of 382 consecutive patients with head and neck squamous cell carcinoma, divided into training (n = 318) and validation (n = 64) cohorts, were retrospectively included. The following PET/CT parameters were analyzed: clinical parameters, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, and distance parameters for the primary tumor and lymph nodes defined by 2 segmentation methods (relative SUVmax threshold and absolute SUV threshold). Cox analyses were performed for OS and DMFS in the training cohort. The concordance index (c-index) was used to identify highly prognostic parameters. These prognostic parameters were externally tested in the validation cohort. Results: In multivariable analysis, the significant parameters for OS were T stage and nodal MTV, with a c-index of 0.64 (P < 0.001). For DMFS, the significant parameters were T stage, nodal MTV, and maximal tumor-node distance, with a c-index of 0.76 (P < 0.001). These combinations of parameters were externally validated, with c-indices of 0.63 (P < 0.001) and 0.71 (P < 0.001) for OS and DMFS, respectively. Conclusion: The nodal MTV associated with the maximal tumor-node distance was significantly correlated with the risk of DMFS. Moreover, this parameter, in addition to clinical parameters, was associated with a higher risk of death. These prognostic factors may be used to tailor individualized treatment.

Le TEP-scanner au 18-FDG est actuellement reconnu comme un examen clef pour le diagnostic des endocardites infectieuses (EI) sur prothèse valvulaire (PV): un hypermétabolisme prothétique constituant désormais un critère majeur de Duke selon l'actualisation des recommandations ESC en 2015. L'intégration du TEP aux critères de Duke permet une meilleure sensibilité (Se) pour le diagnostic d'EI, mais implique une moindre spécificité (Sp), tout en posant le problème de la variabilité inter-observateur. Nous avons étudié l'apport de l'intelligence artificielle (IA) par machine learning (ML) dans la lecture du TEP pour le diagnostic d'EI sur PV. Nous avons inclus sur 3 centres 90 patients ayant bénéficié d'un TEP dans le cadre d'une suspicion d'EI sur PV aortique. Pour chaque patient, une endocarditis team s'est réunie pour retenir ou non le diagnostic d'EI. Les procédés d'IA ont été mis au point en collaboration avec l'Ecole Centrale voisine: 68 patients ont été utilisés pour la cohorte d'entrainement/validation et 22 patients pour la cohorte de test indépendante. Des variables radiomics ont été extraites des volumes TEP puis sélectionnées pour être analysées par un modèle de ML de type Logistic Regression Ridge (LR). Les performances de ML ont d'abord été étudiées sur la cohorte d'entrainement/validation puis sur la cohorte de test. Notre équipe a classé 55 patients en endocardite confirmée et 35 en endocardite rejetée. Le délai moyen entre la réalisation du TEP et la pose de prothèse était de 65,5 mois. 57,8% des patients étaient porteur d'une bioprothèse, 25,6% d'un TAVI et 16,7% d'une PV mécanique. Parmi les EI confirmées, 60% étaient des EI certaines et 40% des EI possibles, avec une documentation à staphylocoque pour 43,6% des patients et à streptocoque pour 18,2% des patients. Le délai moyen entre le TEP et le début des antibiotiques était de 14,1 jours. Le modèle de LR a identifié l'intensité moyenne et l'énergie mesurées sur la PV, la présence d'un hypermétabolisme splénique ou médullaire, et le temps depuis l'initiation des antibiotiques, comme étant positivement corrélés au diagnostic d'EI confirmée. Le délai depuis l'implantation de la PV était négativement corrélé au diagnostic d'EI confirmée. Pour la cohorte d'entrainement/validation, les performances de ML étaient de 65% en Se et 66% en Sp; en prenant en compte les paramètres extra-prothétiques (hypermétabolisme médullaire ou splénique, délai depuis l'implantation de la PV et l'initiation des antibiotiques), les valeurs de Se et Sp étaient respectivement de 73% et 68%. Pour la cohorte de test, en imposant une Sp à 70%, la Se était à 64%, et 60% en prenant en compte les paramètres extra-prothétiques. L'approche de ML a obtenu des résultats acceptables en termes de Se et Sp. Ces données, issues d'une petite cohorte de test, suggèrent que l'IA pourrait apporter une aide au diagnostic d'EI sur PV. Les performances de ML seront prochainement étudiées sur une cohorte de test de plus grande ampleur. Aucun lien d'intérêt

L'immunothérapie a montré une activité clinique durable chez les patients atteints de mélanome métastatique. Cependant, il n'existe aucun marqueur pronostique fiable permettant de définir la réponse à long terme ainsi que le risque de rechute après arrêt du traitement. L'objectif de cette étude était d'évaluer les valeurs prédictives de la TEP-TDM et de la TDM effectuées en fin de traitement sur le risque de rechute après l'arrêt du traitement. Vingt-six patients suivis pour un mélanome métastatique étaient inclus dans cette étude rétrospective. Tous étaient traités par anti-PD1, considérés en rémission complète et avaient bénéficié d'une TDM et d'une TEP-TDM lors de l'arrêt du traitement. Le critère de jugement principal était la survenue d'une rechute après arrêt du traitement. La TDM était interprétée selon les critères RECIST 1.1 : réponse complète (RC), réponse partielle (RP), stabilité (S) et progression (P). Les réponses métaboliques étaient classées en réponse métabolique complète (RMC) lorsque la fixation résiduelle était inférieure à celle du médiastin, réponse métabolique partielle (RMP), stabilité métabolique (SM) et progression métabolique (PM). La durée médiane de traitement était de 7 mois et la médiane de survie sans récidive après arrêt du traitement de 20,5 mois. Selon la TDM de fin de traitement : 9 patients étaient en RC, 15 en RP et 2 en S. Selon la TEP-TDM, 20 patients étaient en RMC et 6 en RMP. Dix patients en RP et 2 en S selon la TDM étaient en RMC sur la TEP-TDM et aucun n'a rechuté lors du suivi. Selon l'évaluation par TEP-TDM: 1/20 patients en RMC a rechuté et 5/6 patients en RMP ont rechuté. Après analyse univariée, une RMP en TEP-TDM était associée de manière significative à une rechute (p = 0,00231) et une RMC à l'absence de rechute (p = 0,00231). La réponse selon les critères RECIST n'était pas associée au risque de rechute (p = 0,862). Après analyse multivariée (ajustement : âge, sexe, RECIST), la TEP-TDM restait pronostique de la rechute (p = 0,015). Nos résultats démontrent la pertinence de la réponse métabolique par rapport à la réponse morphologique pour évaluer une réponse complète et décider d'un arrêt de traitement par anti-PD1 : la plupart de ceux en RP à la TDM sont en RMC selon la TEP-TDM. Après confirmation sur de plus grandes cohortes de patients, la TEP-TDM pourrait donc être l'examen « clé » dans la décision d'arrêt du traitement devant une RMC chez des patients sous anti-PD1.

Background: Timely diagnosis of child physical abuse is of paramount importance. The added value of bone scintigraphy (BS) after a negative radiological skeletal survey (RSS) in children with suspected physical abuse has never been evaluated. Objective: The objective of this study was to assess the extent to which BS could improve the detection rate of skeletal injury in children with suspected physical abuse with an initial negative RSS. Methods: We used discharge codes to retrospectively identify children evaluated for suspected physical abuse in a university hospital (Nantes, France). We included all consecutive children younger than 3 years old who underwent both RSS and BS, with an interval of ≤96 h between tests, from 2013 to 2019. BS and RSS results were interpreted independently during the study period. We specifically analyzed BS results for children with a negative RSS to assess the value of BS as an add-on test. Results: Among the 268 children ≤3 years old with suspected physical abuse who underwent RSS, 140 (52%) also underwent BS within 96 h and were included in the analysis. The median age was 6 months old (interquartile range: 3–8). The detection rate of ≥1 skeletal injury with RSS alone was 49% (n = 69/140, 95% CI: 41–58%) vs. 58% (n = 81/140, 50–66%) with RSS followed by add-on BS, for an absolute increase in the detection rate of 9% points (95% CI: 4–14%). The number of children with a negative RSS who would need to undergo BS to detect one additional child with ≥1 skeletal injury was 6 (95% CI: 4–11). Conclusion: In young children with suspected physical abuse with a negative RSS, add-on BS would allow for a clinically significant improvement in the detection rate of skeletal injuries for a limited number of BS procedures required. Prospective multicenter studies are needed to confirm these findings.

Background Anti-PD1 immunotherapy has shown a sustainable clinical activity in patients with metastatic melanoma. However, strong predictive factors of the long-term response or risk of relapse remain to be identified. Objectives To determine whether FDG-PET imaging could be superior to CT scan in distinguishing residual tumours versus the absence of tumour in patients with a partial response (PR) or stable disease (SD) and whether a complete metabolic response (CMR) was associated with better outcomes. Methods Retrospective study conducted in all patients with metastatic melanoma treated with anti-PD1 immunotherapy between October 2014 and October 2017 considered to be in complete remission. The primary outcome was the occurrence of a relapse during the follow-up. CT scan and FDG-PET scan had to be performed within a maximum of 2 months of treatment discontinuation. For CT imaging, the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 were used and included progressive disease (PD), SD, PR and complete response (CR). For FDG-PET imaging, the metabolic responses were classified as progressive metabolic disease, stable metabolic disease, residual FDG avidity (RFA) and CMR. Results Twenty-six patients were in complete remission after collegial decision. Two patients had a SD on CT scan and a CMR on FDG-PET scan, and none of them relapsed. Ten patients had a PR on CT scan and a CMR on FDG-PET scan, and none of them relapsed. The mean treatment duration to achieve a complete remission was 7 months (3-23). A univariate analysis showed that a RFA assessed on the FDG-PET scan was significantly associated with a relapse (P = 0.00231). Conclusions Most patients with a PR on the CT scan and a CMR on the FDG-PET scan should be considered with a CR. Our study showed that FDG-PET imaging could play a crucial role in predicting the long-term outcome and help to decide whether treatment should be discontinued.

This pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC). Patients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120 nmol of TF2 followed 30 h later by 150 MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up. Eleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98–13.94, SD 3.37], 8.63 cm3 [1.98–46.64; SD 14.83] and 37.90 cm3 [8.07–127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients. This pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance. ClinicalTrials.gov NCT02587247 Registered 27 October 2015

Purpose. - The advent of immunotherapy by checkpoint inhibitor has profoundly changed the prognosis of patients with metastatic melanoma. The objective of our study was to evaluate the prognostic and predictive performance of 18F-FDG PET/CT of the initial extension assessment of stage IIIB-C-D and IV melanomas. Methods. - We retrospectively included 57 patients who had 18F-FDG PET/CT prior to the introduction of anti-PD-1 immunotherapy. The parameters extracted were SUVmax, SUV peak, MTV and TLG of the lesion with highest uptake (MTV LM, TLG LM), as well as MTV total and TLG total, obtained by adaptive segmentation. The18F-FDG PET/CT were dichotomized using the optimal threshold measured according to the area under the curve in the ROC (Receiver Operation Characteristic) curves. These parameters were evaluated using a Cox model. Overall survival and progression-free survival analyses were performed using the Kaplan Meier model. Results. - The median follow-up was 25.4 months, 38 patients had progressed or recurred, and 20 patients had died. TLG LM > 132.59 (P = 0.0011), MTV total > 12 cm(3) (P = 0.0139), and TLG > 94.17 (P = 0.0084) were significantly associated with a shorter progression-free survival. TLG LM > 145.92 (P = 0.0062), MTV total > 10.16 cm(3) (P = 0.0051), and a metastatic spread > 2 organs (P = 0.0001) were associated with a shorter overall survival. Conclusion. - We confirm the potential prognostic interest of PET-TDM at 18FDG before immunotherapy of stage IIIB-C-D and IV melanomas on progression-free survival and overall survival. The combination of these metabolic markers reflecting tumor burden with clinical and biological prognostic factors could allow early identification of patients at high risk of anti-PD-1 failure. (C) 2020 Elsevier Masson SAS. All rights reserved.

Structural valve degeneration (SVD) of bioprostheses is a common and serious complication in patients undergoing aortic valve replacement. SVD pathophysiology remains unclear.18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) have respectively shown that an active metabolic phenomenon of calcification rather than an inflammatory process contribute to native aortic valve stenosis. We studied the respective value of NaF and FDG PET to explore the potential mechanisms involved in SVD. SVD patients underwent NaF PET to explore potential active calcification process, FDG PET to explore potential inflammatory process and thoracic CT. Tracer uptake was quantitatively measured by the bioprosthesis tissue-to-background ratio of standardized uptake values (TBR). Echocardiographic parameters, bioprosthesis calcium scoring on CT, and qualitative pattern of NaF and FDG activity on bioprostheses were analyzed. Twenty-one patients were included. Calcium score was higher in patients with significant NaF visual uptake versus patients without (1065 ± 505 vs. 462 ± 320, P = 0.015). The median NaF TBR (3.49, [2.33–5.04]) was significantly higher than FDG (1.34, [1.20–1.47]). Patients with NaF TBR greater than the median value had a higher calcium score (1059 ± 550 vs. 566 ± 363, P = 0.05), and showed a tendency to have more severe hemodynamic stenosis. Picture shows an example of patient with SVD (A); CT (B) established localizations of calcium deposits; NaF PET/CT (C) show intense uptake adjacent to calcifications; FDG PET/CT (D) show no uptake (Fig. 1). These results suggest a link between SVD severity and active calcification activity and opens new perspectives on the assessment of SVD pathophysiology through NaF PET quantification of ongoing mineral burden.

121 Purpose: Selective internal radiation therapy (SIRT) with yttrium-90 (90Y) is a valuable treatment in unresectable intrahepatic cholangiocarcinoma (ICC). Despite being a fundamental tool for this technique, a very sparse number of studies reported the value of dosimetry in this pathology. This work aimed to evaluate the agreement between technetium-99 (99mTc)-labeled macroaggregated albumin (MAA) SPECT/CT predictive dosimetry and 90Y PET/CT post-treatment dosimetry, and to assess the added value to predict response in ICC patients. Methods: We retrospectively compared the 99mTc-MAA SPECT/CT results of 19 treatment sessions (16 patients, 65 tumors) with 90Y-SIRT using glass microspheres and the post-treatment 90Y PET/CT data. Dose Volume Histograms (DVHs) derived from both modalities were calculated using Kernel based convolution (KBC) and Local Deposition Method (LDM). Absorbed dose (AD) using SPECT/CT data were computed using both relative (SPECTrel) and absolute (SPECTabs) normalization. A rigid registration between SPECT/CT and PET/CT was performed. The correlation of AD to tumors and whole liver normal tissue before and after treatment was assessed using the Mann-Whitney U test associated with the Lin’s concordance index. The significance of prognostic factors was tested using a univariate binary logistic regression at both lesion and patient levels. A sub-cohort of 35 lesions which had a volume > 10cm3 was also studied to minimize registration error and partial volume effect. Survival analysis was conducted through both univariate and multivariate Cox proportional-hazards ratio analyses with a variable selection performed with the elastic-net Cox regression model. Results: Median injected activity was 2.37 GBq (range 0.43-4.19). Mean tumor AD was 242+/- 121 Gy. Unlike SPECTabs-based computation, all AD metrics calculated using SPECTrel, regardless of the computation method, showed a good correlation when comparing with PET-based computation (p > 0.05 and ρc > 0.8). Computation using KBC and LDM exhibited a very high concordance (ρc > 0.99). Median overall-survival was 13.7 months (range: 1.39-39.06) and median progression-free-survival (PFS) was 12.1 months (range: 1.39 - 39.06). No permanent liver toxicities were observed. Ten lesions presented complete response (15%), 42 partial response (65%) and 13 stable disease (20%) according to mRECIST criteria. No progressive lesion was recorded. At a patient level analysis, only the tumor volume and the bi-lobar involvement were significantly associated with response at univariate analysis. No threshold was found between tumor AD and response. However, several DVH-based metrics were significantly higher in the responding lesions than in the non-responding ones using SPECT-based or PET-based data (namely: D95, D70, V50, V30 and dose coefficient of variation). This holds true for only SPECT-based data when considering lesions with volume greater than 10 cm3. Only ECOG was significantly associated with PFS at a multivariate analysis while no variables were retained for the OS analysis. No dosimetric variable was significantly associated with survival. Conclusions: 99mTc-MAA SPECTrel data showed a high concordance with 90Y PET/CT data in ICC tumors and particularly for large lesions (volume > 10 cm3). DVH calculated from SPECT proved to be valuable to estimate tumor response. These preliminary results paved the way to a new workflow for the computation of the required injected activity. Supplementary data including more patients will be presented at the meeting.

Abstract Purpose: To assess the prognostic value of interim 18F-fluorodeoxyglucose (FDG)-PET analysis using decrease in maximum standardized uptake value (SUVmax) versus visual analysis in patients with multiple myeloma. Patients and Methods: We evaluated the prognostic value of FDG-PET after three cycles of lenalidomide, bortezomib, and dexamethasone (RVD) in patients with FDG-avid multiple myeloma included in the French prospective multicenter IMAJEM study. All images were centrally reviewed and interpreted using visual criteria and maximal standardized uptake value reduction (ΔSUVmax). Known prognostic factors, such as the revised International Staging System and biochemical response after three cycles of chemotherapy, were also evaluated. Results: In the multivariate analysis, only ΔSUVmax [P < 0.001, HR = 5.56; 95% confidence interval (CI), 1.96–15.81] and biochemical response after three cycles of RVD (P = 0.025, HR = 0.29; 95% CI, 0.1–0.85) appeared as independent prognostic factors, with a more discriminative HR for ΔSUVmax. ΔSUVmax analysis (>–25% vs. ≤–25%) identified patients with improved median progression-free survival (22.6 months and not reached, respectively). Conclusions: ΔSUVmax appears to be a powerful tool for the prediction of long-term outcome in patients with FDG-avid multiple myeloma. Other prospective studies are needed to further validate this prognostic biomarker. Clin Cancer Res; 24(21); 5219–24. ©2018 AACR.

Le sarcome d’Ewing (SEW) et l’ostéosarcome (OST) sont les tumeurs osseuses les plus fréquentes de l’enfant. Malgré une amélioration constante de la survie, la détermination de facteurs pronostiques pertinents pour identifier les enfants qui développeront une maladie plus agressive est essentielle dans cette pathologie. Néanmoins, à l’exception de la présence d’une maladie métastatique au diagnostic et de la réponse tumorale histopathologique après chimiothérapie néoadjuvante (CHT), la valeur pronostique des autres facteurs proposés varie selon les études. De plus, la plupart de ces études ont exploré des populations hétérogènes mélangeant différents sous-types histologiques, schémas de CHT ou groupes d’âge. Le but de ce travail rétrospectif était d’évaluer la valeur pronostique des indices quantitatifs dérivés de la TEP-FDG réalisée avant et après CHT, sur la réponse histologique et la survie, dans une population pédiatrique homogène. Soixante-deux enfants (31 SEW et 31 OST) ont été inclus. Tous les patients ont été traités par CHT et chirurgie. Des TEP-FDG ont été réalisées au diagnostic et après CHT. Plusieurs paramètres ont été évalués : SUVmax, SUVpeak, SUVmean, MTV, TLG, rapport tumeur-sur bruit-de-fond, 7 paramètres d’analyse de textures et 3 paramètres d’analyse de forme. La segmentation a été réalisée en utilisant une approche adaptative. Les valeurs absolues obtenues sur chacun des examens ainsi que la différence ont été comparées à la régression histopathologique de la tumeur réséquée et au suivi clinique pour l’évaluation de la survie. Chez les patients SEW, aucun des indices quantitatifs considérés n’a montré de valeur pronostique sur la réponse histologique comme sur la survie selon les données de l’analyse univariée. Chez les patients OST, un seul des paramètres de forme appelé élongation, était significativement associé à la PFS et à l’OS lors des analyses univariée et multivariée. Chez les patients pédiatriques présentant un OST, seule l’élongation déterminée sur la TEP-FDG initiale semble avoir une valeur pronostique sur la PFS et l’OS. Contrairement à ce qui était démontré dans les études récentes faites dans des populations adultes, aucun des paramètres étudiés n’a de valeur pronostique dans notre population pédiatrique de SEW. Cette observation renforce l’hypothèse selon laquelle les enfants et les adultes présentent des sous-types différents de ces pathologies sarcomateuses.

Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmunotherapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of α and β RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL.